The HIV-1/AIDS pandemic is the foremost infectious disease causing death and morbidity worldwide. The pandemic, which affects primarily young adults between 15 and 40 years of age, is a socio-economic as well as a burning health issue. In the countries of sub-Saharan Africa worst affected by the pandemic, the loss of young adults has impacted upon the economic output from these countries.
An effective approach to curbing the future impact of this viral disease is through the development and delivery worldwide of a safe, effective and affordable vaccine that prevents infection and transmission of the virus.
Also alternative medical treatments to a vaccine exist today. Efficient HIV-1 drugs exist today, but a downside is the immense costs associated with treatment making it less available for underprivileged third world countries and an economic burden for wealthier countries. Another downside of current treatments is the development of drug resistance. Consequently the drugs are only life prolongers and not an absolute cure. The best strategy to prevent an HIV-1 pandemic, resulting in AIDS patients, would most likely be an effective vaccine. This has been a highly prioritized research field for over 30 years but there is still no working vaccine in sight.
Typically, since a natural defense mechanism of humans and animals against viral diseases is based on a production of protective antibodies, a primary function of many vaccines against such diseases has been to elicit protective antibodies against infectious agents or parts thereof.
Since the discovery of HIV-1 in 1984, efforts to develop a prophylactic vaccine against HIV-1/AIDS infection have been intense and it is now clear that this is an unprecedented vaccine challenge. Due to the extreme genetic variability of HIV-1, a successful vaccine would need to elicit high-titer neutralizing antibodies not only against one or a few virus strains but against the enormous breadth of genetic diversity that exists among circulating viral variants, so-called broadly neutralizing antibodies (bNAbs). This is only possible if conserved and exposed viral determinants are targeted by the immune response. A further challenge with HIV-1 is that the envelope glycoprotein (Env) spikes are unstable complexes and vaccine candidates where stable spikes that preserve, or sufficiently well mimic, the native conformation of the full-length functional HIV-1 spike were so far not developed. This is likely to be a major reason for the failure of most HIV vaccine candidates developed so far.
Although the vaccine field waits for a breakthrough a lot of information has recently been gained about broadly neutralizing antibodies (bnAb). BnAb are antibodies that have been found in some HIV-1 infected persons and they are of high interest because they, binds to and, prevent most viral strains to enter target cells. These results have shown it possible for an individual's immune system to evolve a working antibody response towards HIV-1. But, still no vaccine approach has been able to generate bnAb that targets the HIV-1 virus in humans.